Cerebral palsy (CP) encompasses a group of disorders of movement and posture, attributed to non-progressive disturbances affecting the developing brain. Movement and tone disorders in children and young adults with CP are a great source of disability. CP is the most common cause of acquired dystonia in childhood, but its management is problematic, as medications and neurotoxin denervation only provide modest benefit. Deep brain stimulation of basal ganglia or thalamic targets has a major role in the treatment of isolated dystonias, but its efficacy in dystonic CP (DCP) is much lower. Lower efficacy may be due to structural damage in basal ganglia and motor thalamus, lack of improvement of comorbid choreoathetosis and spasticity, and an increased risk of hardware complications in this population. We propose an alternative brain target for DBS in DCP, the cerebellum, leveraging recent developments in dystonia neurophysiology, brain stimulation hardware and neuroimaging. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a prominent role in contemporary network models of dystonia, and small studies have shown promise of cerebellar stimulation in improving spasticity and CP-related movement disorders. Ten children and young adults with CP and disabling movement disorders and spasticity will undergo bilateral DBS in dorsal (motor) dentate nucleus, with the most distal contact in superior cerebellar peduncle. We will implant Medtronic PerceptTM, an FDA-approved “bidirectional” neurostimulator that can sense and store brain activity as well as simultaneously deliver DBS therapy. Recent improvements in hardware size and brain lead fixation address the prior high complication rate reported for pediatric DBS, and provide “directional” leads for more targeted stimulation. We will characterize abnormal patterns of cerebellar oscillatory activity as measured by local field potentials (LFP) related to clinical assessments and wearable monitors, and their relation to stimulation (Aim 1). Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS (Aim 2). In Aim 3, we will test the efficacy of cerebellar stimulation for improving quality of life as well as motor outcomes as assessed by clinical assessments and objective kinematic metrics. We will use a N-of-1 clinical trial design to mitigate the variability in clinical features in this population. Our goal is to develop a neuromodulation therapy that produces meaningful changes in function and well-being of people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcome useful in planning further studies.
